biostudies-literatureUnknown4(12)Okada MThrombomodulin functions as an anticoagulant through thrombin binding and protein C activation. We herein report the first case of hereditary functional thrombomodulin deficiency presenting with recurrent subcutaneous hemorrhage and old cerebral infarction. The patient had a homozygous substitution of glycine by aspartate at amino acid residue 412 (Gly412Asp) in the thrombin-binding domain of the thrombomodulin gene (designated thrombomodulin-Nagasaki). In vitro assays using a recombinant thrombomodulin with the same mutation as the patient showed a total lack of thrombin binding and activation of protein C and thrombin-activatable fibrinolysis inhibitor (TAFI). Marked clinical and laboratory improvement was obtained with recombinant human soluble thrombomodulin therapy.Blood advances2631-2639https://www.ebi.ac.uk/biostudies/studies/S-EPMC7322956biostudies-literatureA case of thrombomodulin mutation causing defective thrombin binding with absence of protein C and TAFI activation.PMC7322956Moriuchi HAkita NOkada MHayashi TNishioka JSuzuki KHonda GTominaga NfalseA case of thrombomodulin mutation causing defective thrombin binding with absence of protein C and TAFI activation.Thrombomodulin functions as an anticoagulant through thrombin binding and protein C activation. We herein report the first case of hereditary functional thrombomodulin deficiency presenting with recurrent subcutaneous hemorrhage and old cerebral infarction. The patient had a homozygous substitution of glycine by aspartate at amino acid residue 412 (Gly412Asp) in the thrombin-binding domain of the thrombomodulin gene (designated thrombomodulin-Nagasaki). In vitro assays using a recombinant thrombomodulin with the same mutation as the patient showed a total lack of thrombin binding and activation of protein C and thrombin-activatable fibrinolysis inhibitor (TAFI). Marked clinical and laboratory improvement was obtained with recombinant human soluble thrombomodulin therapy.2020-01-01T00:00:00Z2020 Jun2024-11-15T13:25:28.307Z2020-07-04T07:12:19ZS-EPMC73229563255628410.1182/bloodadvances.2019001155